The central goal of the research proposed in this application is the development of novel procedures for the synthesis of antibody conjugates employing solid-phase methodology. The new solid- phase methods described herein will circumvent inherent disadvantages of the current fluid-phase procedures for immunoconjugate synthesis with heterobifunctional crosslinking reagents. The new solid-phase methods will allow the synthesis of immunoconjugates containing the two reactants at a predetermined ratio (usually 1:1) with the least possible inactivation of the two components. As a result, immunoconjugates prepared by the solid-phase methodology can be expected to show the best possible in vivo activities. The solid-phase synthesis will require the development of a novel class of crosslinking molecules: heterotrifunctional reagents. One of the reactive groups of these reagents will serve to immobilize the cross-linker molecule onto solid support matrix while the other two different reactive groups will cross-link the two compounds to be coupled. The heterotrifunctional reagents described are designed to allow the release of the conjugate from the support matrix after completion of the cross-linking reaction without affecting the properties of the coupled components. Two different types of heterotrifunctional crosslinking reagents will be synthesized and used to generate antibody conjugates with cobra venom factor (CVF) and the antineoplastic agent daunorubicin. Reaction rates, the yield of conjugates, and the ratio of the two reactants in the conjugates will be determined under different conditions. The properties of the different immunoconjugates synthesized by solid-phase methodology will be compared with corresponding immunoconjugates synthesized by the traditional fluid-phase procedures. In vitro properties to be analyzed include a) the individual activities of the two components of the conjugates, and b) the cytotoxic activity of the conjugates for antigen-positive target cells. In vivo properties of the conjugates to be analyzed include the stability, plasma half- life, and biodistribution in normal mice.